Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites
peer-reviewed
Erstveröffentlichung
2017-01-23Authors
Braig, David
Nero, Tracy L.
Koch, Hans-Georg
Kaiser, Benedict
Wang, Xiaowei
Wissenschaftlicher Artikel
Published in
Nature Communications ; 8 (2017). - Art.-Nr. 14188. - eISSN 2041-1723
Link to original publication
https://dx.doi.org/10.1038/ncomms14188Institutions
UKU. Klinik für Unfall-, Hand-, Plastische- und WiederherstellungschirurgieDocument version
published version (publisher's PDF)Abstract
C-reactive protein (CRP) concentrations rise in response to tissue injury or infection. Circulating pentameric CRP (pCRP) localizes to damaged tissue where it leads to complement activation and further tissue damage. In-depth knowledge of the pCRP activation mechanism is essential to develop therapeutic strategies to minimize tissue injury. Here we demonstrate that pCRP by binding to cell-derived microvesicles undergoes a structural change without disrupting the pentameric symmetry (pCRP*). pCRP* constitutes the major CRP species in human-inflamed tissue and allows binding of complement factor 1q (C1q) and activation of the classical complement pathway. pCRP*–microvesicle complexes lead to enhanced recruitment of leukocytes to inflamed tissue. A small-molecule inhibitor of pCRP (1,6-bis(phosphocholine)-hexane), which blocks the pCRP–microvesicle interactions, abrogates these proinflammatory effects. Reducing inflammation-mediated tissue injury by therapeutic inhibition might improve the outcome of myocardial infarction, stroke and other inflammatory conditions.
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https://static-content.springer.com/esm/art%3A10.1038%2Fncomms14188/MediaObjects/41467_2017_BFncomms14188_MOESM1199_ESM.pdfSubject headings
[GND]: C-reaktives Protein | Endothelzelle | Herzinfarkt | Komplement <Immunologie>[MeSH]: C-reactive protein | Endothelial cells | Myocardial infarction | Serum amyloid P-component | Complement system proteins
[Free subject headings]: artificial phosphatidylcholine bilayers | amyloid p component | directed mutagenesis | human pentraxins | apoptotic cells | globular head | complement
[DDC subject group]: DDC 610 / Medicine & health
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Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-49033
Braig, David et al. (2023): Transitional changes in the CRP structure lead to the exposure of proinflammatory binding sites. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-49033
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